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Selenocompounds and Sepsis - Redox Bypass Hypothesis: Part B-Selenocompounds in the Management of Early Sepsis

par Forceville, Xavier;Van Antwerpen, Pierre ;Annane, Djillali;Vincent, Jean Louis
Référence Antioxidants & redox signalling, 37, 13-15, page (998-1029)
Publication Publié, 2022-11-01

Article révisé par les pairs

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Résumé :

Significance: Endothelial barrier damage, which is in part caused by excess production of reactive oxygen, halogen and nitrogen species (ROHNS), especially peroxynitrite (ONOO-), is a major event in early sepsis and, with leukocyte hyperactivation, part of the generalized dysregulated immune response to infection, which may even become a complex maladaptive state. Selenoenzymes have major antioxidant functions. Their synthesis is related to the need to limit deleterious oxidant redox cycling by small selenocompounds, which may be of therapeutic cytotoxic interest. Plasma selenoprotein-P is crucial for selenium transport from the liver to the tissues and for antioxidant endothelial protection, especially against ONOO-. Above micromolar concentrations, sodium selenite (Na2SeO3) becomes cytotoxic, with a lower cytotoxicity threshold in activated cells, which has led to cancer research. Recent Advances: Plasma selenium (<2% of total body selenium) is mainly contained in selenoprotein-P, and concentrations decrease rapidly in the early phase of sepsis, because of increased selenoprotein-P binding and downregulation of hepatic synthesis and excretion. At low concentrations, Na2SeO3 acts as a selenium donor, favoring selenoprotein-P synthesis in physiology, but probably not in the acute phase of sepsis. Critical Issues: The cytotoxic effects of Na2SeO3 against hyperactivated leukocytes, especially the most immature forms that liberate ROHNS, may be beneficial, but they may also be harmful for activated endothelial cells. Endothelial protection against ROHNS by selenoprotein-P may reduce Na2SeO3 toxicity, which is increased in sepsis. Future Direction: The combination of selenoprotein-P for endothelial protection and the cytotoxic effects of Na2SeO3 against hyperactivated leukocytes may be a promising intervention for early sepsis. Antioxid. Redox Signal. 37, 998-1029.